Controlled experiments are being conducted to study the efficacy of topical and systemic vitamin A therapy in ameliorating a spontaneous inherited corneal dystrophy which resembles human keratomalacia in an inbred mouse strain. Corneas from these animals, normal animals, vitamin A deficient animals and human donors are being radioactively labeled in organ culture to determine the influence of vitamin A therapy on glycoconjugate synthesis and on collagenase activity. Mouse corneas have also been characterized by scanning and transmission electron microscopy. Results indicate that the epithelium of the dystrophic mouse cornea elaborates an unusual basement membrane. Vitamin A stimulates the synthesis of a major high molecular weight epithelial glycoprotein but does not appear to affect the course of the corneal destructive process in controlled therapeutic trials. Normal human and keratoconus corneas are being maintained in organ culture to determine the types of collagen-specific metalloenzymes elaborated and to search for inhibitors of collagenase.